Genetic study identifies novel genes in developmental dysplasia of the hip

Publication type

Journal Article

Authors

Publication date

March 31, 2026

Summary:

Developmental dysplasia of the hip (DDH), a morphological abnormality of the hip joint, is a well-recognized risk factor for hip osteoarthritis (OA). Much remains unknown about the genetic factors of DDH and its subtypes. To further understand its genetic basis, we conducted genome-wide association studies (GWASs) using a total of 1 085 Japanese DDH cases (including 788 hip dysplasia cases without dislocation and 297 cases with dislocated hip) and 24 000 controls. Additionally, we meta-analyzed with United Kingdom (UK) DDH GWAS and the largest hip OA GWAS to date. We identified three genome-wide significant novel loci, COL11A2, CALN1 and TRPM7, associated with hip dysplasia without dislocation. None of these signals were significant in dislocated hips, and additionally two of the signals had an opposite direction of association, suggesting distinct genetic architectures between the subtypes. The Japanese DDH GWAS identified five associated loci (VEGF-C, FOXC1, SMC2, SLC38A4, and TRPM7), and the trans-ancestry meta-analysis with UK revealed two loci (COL11A1 and GDF5) supported by strong trans-ancestry genetic correlation (r = 1.0). In total, nine loci were identified for DDH and its subtypes, with hip dysplasia without dislocation showing distinct genetic signals from hip dislocation. The meta-analysis of DDH and hip OA identified five novel signals for hip OA. Susceptibility loci and heritability enrichment analyses implicated pathways involving bone formation, collagen type XI trimer, and chondrocyte development, as well as their gene regulation, in DDH. These findings enhance understanding of the genetic architecture and biological pathways underlying DDH, providing new insights into its relationship with OA.

Published in

Bone Research

Volume

Volume: 14:34

DOI

https://doi.org/10.1038/s41413-026-00514-8

ISSN

20954700

Subjects

Notes

© The Author(s) 2026

Open Access

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Code: For the codes for statistical analyses, we followed the publicly available codes and the instructions, which are provided by the following statistical tool website: PLINK1.9 (https://www.cog-genomics.org/plink/), PLINK2.0 (https://www.cog-genomics.org/plink/2.0/), SAIGE (https://github.com/we izhouUMICH/SAIGE), METAL (https://github.com/statgen/METAL), Fine Mapping (Wakefield Method, https://rdrr.io/cran/gtx/man/abf.Wakefield.html), LDSC (https://github.com/bulik/ldsc), Popcorn (https:// github.com/brielin/Popcorn), LocusZoom (http://locuszoom.org/), FUMA (https://fuma.ctglab.nl/). No custom codes were generated for the present study.

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